It is known that creating a vortex in fluids contained in a vessel is an effective means for mixing the fluid. Common laboratory vortexers use a support cup or a resilient vessel and engage the bottom of the vessel with a receiving surface mounted eccentrically to a motor. This translates the lower end of the vessel in a circular path or orbit at a high speed and thereby creates an effective vortex in the fluid contained in the vessel. Exemplary of this type of device are those disclosed in U.S. Pat. Nos. 4,555,183 (Thomas) and 3,850,580 (Moore et al.). These devices are manual in that an operator is required to hold the vessel in contact with the eccentrically movable means to create the vortex in the fluid disposed in the vessel.
Such vortex type devices would be extremely advantageous if used in an automated chemical analysis instrument as it is noninvasive and therefore can avoid the concern of contamination associated with an improperly cleaned invasive mixing means.
A device that incorporates this type of mixing into an automated testing apparatus is disclosed in an article by Wada et al. entitled "Automatic DNA Sequencer: Computer-programmed Microchemical Manipulator for the Maxam-Gilbert Sequencing Method", Rev. Sci. Instrum. 54(11), November 1983, pages 1569-1572. In the device disclosed in this article, a plurality of reaction vessels are held flexibly in a centrifuge rotor. A rotational vibrator is mounted on a vertically moving cylinder. When mixing is desired, the reaction vessel is positioned in a mixing station directly above the rotational vibrator. The vertically movable cylinder is moved upwardly to contact the bottom of the reaction vessel with a rotary, vibrating rubber portion. The rotational vibrator is then actuated to create the vortex in the fluid contained in the vessel.
This device has the shortcoming that two degrees of motion are required to create a vortex in a reaction vessel located at a mixing station the rotary motion of the vibrator and the linear motion of the vertically moving cylinder. This requires two separate actuators as well as the additional position sensors and software to properly control them. These extra elements equate to an inherently greater cost and lower reliability than a device that could perform the same function utilizing a single degree of motion.
This is of particular significance in a serial processing chemical analysis instrument in which a plurality of mixing stations are required. In serial instruments, reaction vessels are stepped or indexed through various processing positions such as add sample and/or reagent incubate, wash, mix, etc. Such mixing is desirable in most automated chemical analyzers and can become necessary when solid supports such as glass beads or magnetic particles are used that often have a tendency to sink to the bottom of the reaction vessel.
For example, in heterogeneous immunoassays, magnetic particles can be used as the basis for separation of reagents from ligand-antibody bound particles. A particularly desirable particle is disclosed in U.S. Pat. No. 4,661,408 (Lau et al.). These particles have a tendency to settle at a rate which can be detrimental to the kinetics of the reaction. It is therefore desirable that the reaction mixture be mixed regularly during incubation while the reaction is occurring. One mixer that overcomes many of the disadvantages of the prior art is that described in U.S. Pat. No. 4,848,917 issued July 18, 1989 to E. I. du Pont de Nemours and Company. This patent describes a vortexing mixer drive that has a rotatable coupling rod where an end face defines an off center countersink with a bore at the center of the countersink. The rod is actually displaced to engage a vessel's protuberant tip to effect rotational motion and thereby nutate the material with the vessel. The disadvantage of this system is that it takes two translators, a rotary translator as well as a linear translator.
Another system is that described in U.S. Pat. No. 4,895,453 issued Jan. 23, 1990 to Devlin et al. This system describes an automatic vortexing drive in which a rotatable coupling has a cuplike recess positioned off of an opening radially outward from the axis of rotation of the coupling. The coupling is positioned to intercept at the lower and reaction vessels in the recess. Selective rotation of the coupling permits the vessels to pass the coupling or be engaged by the coupling and mutated. This system while quite excellent requires somewhat complex controls of the drive mechanism.
Many of these prior art systems in general are seen to have a number of disadvantages; one is that they tend not to be simple and require either a large number of parts or a complex drive system or multiple drive motors. Another is in some cases they do not gently engage the vessels which are to be nutated sometimes causing spillage of the contents of the vessels. Finally, the systems of the prior art do not always reliably engage the vessels to be nutated.